清肠化湿方介导PI3K/AKT/mTOR通路调控自噬治疗溃疡性结肠炎的机制研究

Autophagy is an important mechanism of self protection，playing an important role in the pathogenesis of ulcerative colitis (UC). Recent studies have shown that the activation of PI3K/AKT/mTOR signaling pathway mediates the inhibition of autophagy, which lead to the increase of inflammatory cytokines and the destruction of intestinal mucosal barrier, which is involved in the pathogenesis of UC. Therefore, inhibition of this signaling pathway and induction of autophagy has become a new approach for UC drug discovery. Our previous study found that the treatment of UC with Qingchang huashi formula was significant curative, with the mechanism of inhibition of the PI3K/AKT signaling pathway, reducing intestinal inflammation, promoting intestinal mucosa repair, while need to further clarification is needed to improve the relationship between autophagy and the decoction. Started from research of autophagy, with sulfasalazine, AKT inhibitor Triciribine , mTOR inhibitor rapamycin as control, using the method of in vivo and in vitro experiments combined with the observation of Qingchang Huashi formula mediated regulation of PI3K/AKT/mTOR signaling pathway of autophagy, thus alleviate intestinal mucosal inflammation, repair of gut barrier, thus explains the mechanism the Qingchang huashi formula in treating ulcerative colitis, which provide a new objective basis for the clinical medication, new ideas and the foundation for development of new traditional Chinese medicine for the treatment of UC.

自噬是机体进行自我保护的一种重要机制，在溃疡性结肠炎（UC）的发病中起着重要的作用，最新研究显示自噬抑制可引起肠道炎症因子增多和肠黏膜屏障破坏，且与PI3K/AKT/mTOR信号通路激活有关。因此，抑制该信号通路、诱导自噬成为UC药物研发的新途径。我们前期研究发现清肠化湿方治疗UC疗效显著，其作用机制与抑制PI3K/AKT信号通路，减轻肠道炎症反应、修复肠黏膜有关，但与自噬的关系有待进一步阐明。本课题从自噬入手，以柳氮磺吡啶、AKT抑制剂曲西立滨、mTOR抑制剂雷帕霉素为对照，通过体内和体外实验观察清肠化湿方介导PI3K/AKT/mTOR信号通路对自噬的调控作用，进而减轻肠黏膜炎症、修复肠黏膜屏障，从而阐明清肠化湿方治疗溃疡性结肠炎的机制，为临床用药提供新的客观依据，以及开发治疗UC的中药新药提供新的思路和基础。